on MS: A War on Multiple Fronts....MUST READ

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on MS: A War on Multiple Fronts

Tuesday, June 1, 2004; Page HE05

Until about a decade ago, a list of any year's advances in multiple sclerosis research would be pretty scant. But since the introduction of the first drug therapies for MS -- which transformed it from an untreatable to a treatable disease -- MS research has burgeoned. During the past year alone, so many intriguing developments have been announced that it's hard to keep them straight. It's even harder to keep them in perspective.

MS experts don't always agree on what is most newsworthy, though their assessments often overlap. Three such experts -- Henry McFarland, the National Institutes of Health's top MS doctor, Reingold, vice president for research programs at the National MS Society, and Art Mellor, who founded the Boston Cure Project after being diagnosed with MS in 2000 -- helped compile this list of the past year's key developments.

THE DRUG-TREATMENT FRONT

Reingold cites the importance of long-term studies of existing drug therapies (including the CHAMPIONS study of Avonex and a study of Copaxone conducted by researchers at University of land at Baltimore). They confirm not only that the drugs slow MS's progress, he said, but that they "tend to work better when started early in the disease" and that "the longer you stay on the drugs, the better off you'll be."

Antegren, Biogen's monoclonal antibody designed to keep myelin-destroying immune cells from crossing from the blood to the brain, remains a hot topic as clinical trials (one against placebo, one in combination with Avonex) proceed. McFarland argued that Antegren, delivered via weekly infusion, is "a promising drug" but not necessarily a "major conceptual breakthrough" since its mode of action is similar to that of existing injectable drugs.

Statins -- the drugs already much prescribed for cholesterol reduction -- have shown early promise at reducing the number of brain lesions in MS patients. If that holds up during the larger clinical trials underway, statins could be "relatively exciting," McFarland said, particularly if they're shown to have a different mechanism of action and, perhaps, a capacity to "trigger some reparative mechanism."

An oral immune-modulating drug, laquinir, showed positive results in early clinical trials, as did Zenapax, a monoclonal antibody that interferes with the ability of the messenger chemical interleukin 2 to stimulate destructive immune-cell behavior and thus focuses on "a completely different biological problem" in MS, according to Reingold.

Because cognitive problems affect some 60 percent of people with MS, Reingold said, ongoing trials of Pfizer's Aricept (donepezil), a drug that's shown modest utility in helping Alzheimer's patients retain memory, are of huge interest. But Reingold isn't convinced that the drug will ultimately offer much practical benefit to MS patients, even if clinical-trial participants show improvement in the "fine, precise, minuscule" cognitive measures used in studies.

COURSE-OF-DISEASE FRONT

A study by Mayo Clinic researchers suggested that MS is not as progressively debilitating as has been believed. Less than half the 161 patients who were assessed in 1991 and again in 2001 had developed worsening disability. A separate study showed that patients with optic neuritis, a disruption of vision that's been considered a common early sign of MS, had only a 40 percent chance of progressing to MS after 15 years.

Much-reported findings from an Australian researcher who examined brain MRIs (magnetic resonance images) taken immediately upon the death of a young girl with a rare, rapidly progressing form of MS suggest that the death of brain cells that produce myelin may be the initiating event in MS, not just a result of the immune system's attack, as has been generally believed. Such a finding, if borne out by further research, could upend many basic premises about MS and lead to new treatment approaches. But Reingold and McFarland note that 10 years' experience shows that drug therapies targeting the immune system do modify the disease, which contradicts the new findings' key implication.

Perhaps more useful are ongoing efforts to identify the biological underpinnings of MS's various pathological patterns; three distinct subcategories of the disease -- including one in which inflammation seems to precede nerve damage -- have been described so far. This, coupled with the pursuit of MS biomarkers -- subgroups of proteins and genes whose activities may be involved in triggering the disease -- may help researchers tailor therapies for individual cases.

Reingold points to groundbreaking experimental work involving the purposeful destruction (using chemotherapy) of the MS patient's faulty immune systems and the subsequent replacement of that system with a healthy one. Canadian doctors have performed the high-risk procedure in a small number of patients who hadn't responded to other treatment; its wider application depends on the long-term success of those cases.

Although "we know that vitamin D and sunlight have an immunomodulatory effect," data from this year's ballyhooed reports regarding sun exposure, vitamin D and MS risk "are not terribly convincing" to McFarland. Nonetheless, he said, "the vitamin D pathway may contribute in some way to susceptibility or influencing the course of the disease."

ON OTHER FRONTS

Mellor notes such advances as the introduction of the longer-acting erectile-dysfunction drug Cialis, which addresses a common problem among male MS patients. Mellor also welcomes the Food and Drug Administration's approval of the iBOT wheelchair, which lets users climb stairs and elevate themselves while sitting so their heads are at the same level as those of standing people.

Mellor's keeping an eye on the issue of medicinal use of marijuana, particularly after MS celebrity and talk-show host Montel went public this year with his own use of the drug for MS-related pain.

Also on Mellor's mind: the relabeling of Avonex, which now warns that depression may be a side effect, and a Danish study showing that MS patients whose children died suffered increased relapse rates -- thus strengthening the argument that stress contributes to MS exacerbations.

-- Huget